PRIMOSOMA: COMPONENTS, FUNCTIONS AND APPLICATIONS - BIOLOGY - 2025

A primosome, in genetics, and other branches of biology, is a multiprotein complex in charge of executing the first steps that lead to DNA replication. DNA replication is a complex process that involves several stages, each of them strictly regulated to ensure the fidelity and correct segregation of the generated molecules.

The replicative complex that executes all the replication steps is called the replisome, and the one responsible only for its initiation, the primosome. Only the proteins that remain associated forming a complex multiprotein superstructure belong to these bodies, or somes. However, many other accessory proteins serve additional roles in primosomes.

The primosome must synthesize a small RNA molecule that tells DNA polymerases where to begin de novo DNA synthesis. This small RNA molecule is called the primer (for others, primer), since it primes (that is, it starts) the DNA synthesis reaction.

In Spanish, to prevail means to prevail, to stand out, to predominate or to grant primacy to something or someone. That is, give preference. In English, 'to prime' means to prepare or be ready for something.

In any case, every biological reaction must be governed by something, and DNA replication is no exception.

Components

Generally speaking, each replication fork should recruit at least one primosome. This occurs at a specific place (sequence) in DNA called the ori, by origin of replication.

It is at this site where the specific RNA molecule (primer) must be synthesized that the synthesis of the new DNA will prevail. Regardless of whether the replication is unidirectional (a single replication fork with a single direction) or bidirectional (two replication forks, towards two opposite directions), the DNA must open and "become" a single band.

The so-called leader band (3 'to 5' sense) allows continuous synthesis of DNA in the 5 'to 3' sense, starting from a single DNA: RNA hybrid site.

The retarded band, in the opposite direction, serves as a template for the discontinuous synthesis of new DNA into fractions called Okazaki fragments.

To give rise to each Okazaki fragment, the initiation reaction must be prioritized each time with the same primosomes (probably reused) to form the same type of hybrids.

Premium

RNA primase is a DNA-dependent RNA polymerase; an enzyme that uses DNA as a template to synthesize an RNA complementary to its sequence.

RNA primase, in conjunction with helicase, binds to template DNA and synthesizes a primer or primer 9-11 nt in length. Starting from the 3 'end of this RNA, and by the action of DNA polymerase, a new DNA molecule begins to elongate.

Helicasa

Another fundamental component of the primosome is a helicase: an enzyme capable of unwinding double-band DNA and giving rise to single-band DNA in the area where it acts.

It is in this single band DNA substrate that RNA primase acts to give rise to the primer from which DNA synthesis extends by the DNA polymerase that is part of the replisome.

DNA polymerase

Although for some, by including DNA polymerase, we are already talking about the replisome, the truth is that if DNA synthesis is not started, the reaction has not prevailed. And this is only achieved by the primosome.

In any case, DNA polymerases are enzymes capable of synthesizing DNA de novo from a template that guides them. There are many types of DNA polymerases, each with its own requirements and characteristics.

They all add deoxynucleotide triphosphate to a strand that grows 5 'to 3'. Some, but not all, DNA polymerases have test reading activity.

That is, after adding a series of nucleotides, the enzyme is able to detect erroneous incorporations, locally degrade the affected area and add the correct nucleotides.

¿ Other proteins in the primosome?

Strictly speaking, the enzymes mentioned would suffice to prioritize DNA synthesis. However, other proteins have been found to participate in the assembly and function of the primosome.

The controversy is not easy to resolve because primosomes from different domains of life have distinctive functional capabilities. In addition, the arsenal of RNA cousins ​​should be added those encoded by viruses.

We could conclude that each primosome has the ability to interact with other molecules depending on the function it is going to fulfill.

Other functions of primosomes

It has been found that primosomes can also participate in the polymerization of DNA or RNA molecules, in the terminal transfer of different types of nucleotides, in some DNA repair mechanisms, as well as in the recombination mechanism known as terminal junction of ends. not homologous.

Finally, it has also been observed that primosomes, or at least cousins, could also be involved in the restart of replication at stopped forks.

We could say that in some way the primosomes not only start this fundamental mechanism of DNA metabolism (replication), but also contribute to its control and homeostasis.

Applications

The bacterial primosome is the subject of active research as a target site that could allow the development of more powerful antibiotics. In Escherichia coli, primase is the translational product of the dnaG gene.

Although all living beings use a similar mechanism to initiate DNA replication, the DNA-G protein has characteristics that are its own and unique.

For this reason, biologically active compounds are being designed that would specifically attack the primosome of the bacterium, without affecting the human being victim of a bacterial infection.

The strategy appears to be so promising that research is being directed at other components of the bacterial replisome. Furthermore, inhibition of the primosome primase and helicase of some herpesviruses has provided excellent clinical results in the fight against varicella zoster and herpes simplex viruses.

References

1. Alberts, B., Johnson, AD, Lewis, J., Morgan, D., Raff, M., Roberts, K., Walter, P. (2014) Molecular Biology of the Cell (6 ^th Edition). WW Norton & Company, New York, NY, USA.
2. Baranovskiy, AG, Babayeva, ND, Zhang, Y., Gu, J., Suwa, Y., Pavlov, YI, Tahirov, T.H. (2016) Mechanism of concerted RNA-DNA primer synthesis by the human primosome. Journal of Biological Chemistry, 291: 10006-10020.
3. Kaguni, JM (2018) The macromolecular machines that duplicate the Escherichia coli chromosome as targets for drug discovery. Antibiotcis (Basel), 7. doi: 10.3390 / antibiotics7010023.
4. Lodish, H., Berk, A., Kaiser, CA, Krieger, M., Bretscher, A., Ploegh, H., Amon, A., Martin, KC (2016). Molecular cell biology (8 ^th edition). WH Freeman, New York, NY, USA.
5. Shiraki, K. (2017) Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster. Drugs of Today (Barcelona), 53: 573-584.